ArticleJournal of virology2013
Conformation-dependent recognition of HIV gp120 by designed ankyrin repeat proteins provides access to novel HIV entry inhibitors.
Article in Journal of virology, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 21 papers.
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The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
21 citing papers in PubMed.
- HIV capsid inhibitors: Mechanisms, resistance, and therapeutic advances.PLoS pathogens · 2026Review
- Assessing immunogenicity barriers of the HIV-1 envelope trimer.NPJ vaccines · 2023Article
- Conserved HIV-1 V3 loop helix offers potential for broad neutralization.Nature structural & molecular biology · 2023Article
- Trapping the HIV-1 V3 loop in a helical conformation enables broad neutralization.Nature structural & molecular biology · 2023Article
- Dimeric Ankyrin with Inverted Module Promotes Bifunctional Property in Capturing Capsid to Impede HIV-1 Replication.International journal of molecular sciences · 2023Article
- Review
- DbStRiPs: Database of structural repeats in proteins.Protein science : a publication of the Protein Society · 2022Article
- Virus Entry Inhibitors: Past, Present, and Future.Advances in experimental medicine and biology · 2022Review
- Distinct conformations of the HIV-1 V3 loop crown are targetable for broad neutralization.Nature communications · 2021Article
- Performance of Affinity-Improved DARPin Targeting HIV Capsid Domain in Interference of Viral Progeny Production.Biomolecules · 2021Article
- Nanobodies that Neutralize HIV.Vaccines · 2019Review
- Current Peptide and Protein Candidates Challenging HIV Therapy beyond the Vaccine Era.Viruses · 2017Review
- Rigidly connected multispecific artificial binders with adjustable geometries.Scientific reports · 2017Article
- Delineating CD4 dependency of HIV-1: Adaptation to infect low level CD4 expressing target cells widens cellular tropism but severely impacts on envelope functionality.PLoS pathogens · 2017Article
- Development of peptide inhibitors of HIV transmission.Bioactive materials · 2016Review
- Human Immunodeficiency Virus Immune Cell Receptors, Coreceptors, and Cofactors: Implications for Prevention and Treatment.AIDS patient care and STDs · 2016Review
- Combined Antiviral Therapy Using Designed Molecular Scaffolds Targeting Two Distinct Viral Functions, HIV-1 Genome Integration and Capsid Assembly.Molecular therapy. Nucleic acids · 2015Article
- Improvement of LysM-mediated surface display of designed ankyrin repeat proteins (DARPins) in recombinant and nonrecombinant strains of Lactococcus lactis and Lactobacillus Species.Applied and environmental microbiology · 2015Article
- Receptor binding domain based HIV vaccines.BioMed research international · 2015Review
- Article
Corrections and comments
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Authors and funding
14 authors.
Funding
Abstract
Here, we applied the designed ankyrin repeat protein (DARPin) technology to develop novel gp120-directed binding molecules with HIV entry-inhibiting capacity. DARPins are interesting molecules for HIV envelope inhibitor design, as their high-affinity binding differs from that of antibodies. DARPins in general prefer epitopes with a defined folded structure. We probed whether this capacity favors the selection of novel gp120-reactive molecules with specificities in epitope recognition and inhibitory activity that differ from those found among neutralizing antibodies. The preference of DARPins for defined structures was notable in our selections, since of the four gp120 modifications probed as selection targets, gp120 arrested by CD4 ligation proved the most successful. Of note, all the gp120-specific DARPin clones with HIV-neutralizing activity isolated recognized their target domains in a conformation-dependent manner. This was particularly pronounced for the V3 loop-specific DARPin 5m3_D12. In stark contrast to V3-specific antibodies, 5m3_D12 preferentially recognized the V3 loop in a specific conformation, as probed by structurally arrested V3 mimetic peptides, but bound linear V3 peptides only very weakly. Most notably, this conformation-dependent V3 recognition allowed 5m3_D12 to bypass the V1V2 shielding of several tier 2 HIV isolates and to neutralize these viruses. These data provide a proof of concept that the DARPin technology holds promise for the development of HIV entry inhibitors with a unique mechanism of action.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.